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Enzymology and Molecular Biology of Carbonyl Metabolism 3 pp 293–304Cite as

The Activation of Alcohols by Liver Alcohol Dehydrogenase: Dependence of Inhibition Upon the pKa Lowering Effect

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 284))

Abstract

Liver alcohol dehydrogenase (LADH) is a zinc metalloenzyme that catalyzes the reversible oxidation of alcohols to aldehydes or ketones (Pocker, 1989). The catalytic zinc ion is bound 25 Å from the protein surface at the bottom of a tunnel lined with hydrophobic amino acid residues that stabilize the binding of substrates. For most primary alcohols, including ethanol, the oxidation process follows a compulsory ordered mechanism in which NAD+ binding precedes alcohol binding (Dalziel, 1975). Oxidation occurs within the ternary complex followed by the stepwise release of aldehyde and NADH, respectively.

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References

  • Andersson, P., Kvassman, J., Lindstörm, A., Olden, B. and Pettersson, G., 1981a, Effect of pH on pyrazole binding to liver alcohol dehydrogenase, Eur. J. Biochem. 114: 549.

    Article  PubMed  CAS  Google Scholar 

  • Andersson, P., Kvassman, J., Olden, B. and Pettersson, G., 1981b, Synergism between coenzyme and carboxylate binding in liver alcohol dehydrogenase, Eur. J. Biochem. 118: 119.

    Article  PubMed  CAS  Google Scholar 

  • Ballinger, P., and Long, F.A., 1960, Acid ionization constants of alcohols. II. Acidities of some substituted methanols and related compounds, J. Am. Chem. Soc. 82: 795.

    Article  CAS  Google Scholar 

  • Dalziel, K., 1975, Kinetics and mechanism of nicotinamide-nucleotide-linked dehydrogenases, The Enzymes (Boyer, P.D., ed) 3rd edn., 11: 1.

    Article  CAS  Google Scholar 

  • Dalziel, K., 1963, The purification of nicotinamide adenine dinucleotide and the kinetic effects of nucleotide impurities, J. Biol. Chem. 238: 1538.

    PubMed  CAS  Google Scholar 

  • Eklund, H., and Brändén, C.-I., 1987, Alcohol dehydrogenase, Biological Macromolecules and Assemblies (Jurnak, F. and McPherson, A., eds) 3:73.

    Google Scholar 

  • Eklund, H., Plapp, B.V., Samama, J.-P., and Brändén, C.-I., 1982, Binding of substrate in a ternary complex of horse liver alcohol dehydrogenase, J. Biol. Chem. 257: 14349.

    PubMed  CAS  Google Scholar 

  • Evans, S.A. and Shore, J.D., 1980, The role of zinc-bound water in liver alcohol dehydrogenase catalysis, J. Biol. Chem. 255: 1509.

    PubMed  CAS  Google Scholar 

  • Greeves, M.A., Koerber, S.C., Dunn, M.F., and Fink, A.L., 1983, The effect of cryosolvents on the spectral and catalytic properties of liver alcohol dehydrogenase, J. Biol. Chem. 258: 12184.

    Google Scholar 

  • Kvassman, J., and Pettersson, G., 1980, Unified mechanism for proton-transfer reactions affecting the catalytic activity of liver alcohol dehydrogenase, Eur. J. Biochem. 103: 565.

    Article  PubMed  CAS  Google Scholar 

  • Makinen, M.W., Maret, W., and Yim, M.B., 1983, Neutral metal-bound water is the base catalyst in liver alcohol dehydrogenase, Proc. Nacl. Acad. Sci. 80: 2584.

    Article  CAS  Google Scholar 

  • Mannervik, B., 1981, Design and analysis of kinetic experiments for discrimination between rival models, Kinetic Data Analysis (Endrenyi, L., ed) p. 235.

    Google Scholar 

  • Maret, W., and Zeppezauer, M., 1986, Influence of anions and pH on the conformational change of horse liver alcohol dehydrogenase induced by binding of oxidized nicotinamide adenine dinucleotide: binding of chloride to the catalytic metal ion, Biochemistry 25: 1584.

    Article  PubMed  CAS  Google Scholar 

  • Mildvan, A.S., and Weiner, H., 1969, Interaction of a spin-labeled analog of nicotinamide-adenine dinucleotide with alcohol dehydrogenase. II. Proton relaxation rate and electron paramagnetic resonance studies of binary and ternary complexes, Biochemistry 8: 552.

    Article  PubMed  CAS  Google Scholar 

  • Pavelich, W.A., and Taft, R.W., 1957, The evaluation of inductive and steric effects on reactivity. The methoxide ion-catalyzed rates of methanolysis of 1-menthyl esters in methanol, J. Am. Chem. Soc. 79: 4935.

    Article  CAS  Google Scholar 

  • Pocker, Y., 1989, Alcohol dehydrogenase: structure, catalysis, and site-directed mutagenesis, Metal Ions in Biological Systems (Sigel, H., ed) 25: 336.

    Google Scholar 

  • Pocker, Y., Li, H., and Page, J.D., 1987, Liver alcohol dehydrogenase: metabolic and energetic aspects, Alcohol and Alcoholism, Suppl. 1: 181.

    CAS  Google Scholar 

  • Pocker, Y., and Raymond, K.W., 1985, Liver alcohol dehydrogenase: substrate inhibition and competition between substrates,Alcohol 2 3.

    Google Scholar 

  • Sartorius, C., Martin, G., Zeppezauer, M., and Dunn, M.F., 1987, Active-site cobalt(II)-substituted horse liver alcohol dehydrogenase: characterization of intermediates in the oxidation and reduction processes as a function of pH, Biochemistry 26: 871.

    Article  PubMed  CAS  Google Scholar 

  • Sekhar, C.V., and Plapp, B.V., 1990, Rate constants for a mechanism including intermediates in the interconversion of ternary complexes by horse liver alcohol dehydrogenase, Biochemistry ,29, 4289.

    Article  PubMed  CAS  Google Scholar 

  • Shore, J.D., and Theorell, H., 1966, Substrate inhibition effects in the liver alcohol dehydrogenase reaction, Arch. Biochem. Biophy. 117, 375.

    Article  CAS  Google Scholar 

  • Shore J.D., Gutfreund, H., Brooks, R.L., Santiago, D., and Santiago, P., 1974, Proton equilibria and kinetics in the liver alcohol dehydrogenase reaction mechanism, Biochemistry 13, 4185.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, S., Cohen, L.A., Miller, H.K., and Peake, E., 1971, Calculation of the pKa values of alcohols from * constants and from their carbonyl frequencies of their esters, J. Org. Chem. 36: 1205.

    Article  CAS  Google Scholar 

  • Theorell, H., and McKinely-McKee, J.S., 1961, Liver alcohol dehydrogenase. III. Kinetics in the presence of caprate, isobutyramide and imidazole, Acta Chem. Scand. 15: 1811.

    Article  CAS  Google Scholar 

  • Theorell, H., and Yonetani, Y., 1962, Spectrophotometric demonstration of ternary liver alcohol dehydrogenase-coenzyme-substrate complexes, Arch. Biochem. Biophys.,Suppl. 1: 209.

    Google Scholar 

  • Theorell, H., and Yonetani, Y., 1963, Liver alcohol dehydrogenase-DPN-pyrazole complex: a model of a ternary intermediate in the enzyme reaction, Biochem. Z. 338: 537.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Chemistry, University of Washington, Seattle, WA, 98195, USA

    Y. Pocker & Joe D. Page

Authors
  1. Y. Pocker
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  2. Joe D. Page
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Editor information

Editors and Affiliations

  1. Department of Biochemistry, Purdue University, West Lafayette, Indiana, 47907, USA

    Henry Weiner

  2. Chemisches Zentrallabor, Inselspital, Bern, CH 3010, Switzerland

    Bendicht Wermuth

  3. Indiana University School of Medicine and Veterans Administration Medical Center, Indianapolis, Indiana, 46202, USA

    David W. Crabb

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© 1990 Plenum Press, New York

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Pocker, Y., Page, J.D. (1990). The Activation of Alcohols by Liver Alcohol Dehydrogenase: Dependence of Inhibition Upon the pKa Lowering Effect. In: Weiner, H., Wermuth, B., Crabb, D.W. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 3. Advances in Experimental Medicine and Biology, vol 284. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5901-2_32

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  • DOI: https://doi.org/10.1007/978-1-4684-5901-2_32

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5903-6

  • Online ISBN: 978-1-4684-5901-2

  • eBook Packages: Springer Book Archive

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